Efficacy of varenicline versus bupropion for smoking cessation: A systematic review and meta-analysis of randomized controlled trials.

According to the Global Burden of Disease (GBD) Study conducted in 2019, smoking tobacco leads to over 8 million deaths each year. Hence, it is crucial to identify optimal smoking cessation therapy. To compare the efficacy of varenicline versus bupropion for smoking cessation by performing a meta-analysis of randomized controlled trials (RCTs). Protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). The Patient intervention comparison outcome time (PICOT) format is used in the study. Patients having nicotine use disorder treated with varenicline or bupropion were included, and the continuous abstinence rate (CAR) was assessed at 12, 24, and 52 weeks. The PubMed and Google Scholar databases were systematically searched, and after the screening, RCTs involving a comparison of varenicline and bupropion in smoking cessation were included. We performed a meta-analysis of three RCTs (10110 patients) by RevMan 5.4.1 statistical software to determine the efficacy of varenicline compared with bupropion in smoking cessation. The CAR at 9- to 12-week follow-up of varenicline is superior to bupropion (OR = 1.79, CI range: 1.59-2.02, P < 0.001). Similarly, the CAR of varenicline is superior to bupropion for weeks 9-24 (1.51, 1.32 to 1.72) and weeks 9-52 (1.60, 1.22 to 2.12), suggesting the absolute advantage of varenicline over bupropion for smoking cessation in terms of efficacy. Both varenicline and bupropion are efficacious therapies for smoking cessation. Compared with bupropion, varenicline can significantly improve the CAR at the end of treatment, at 24 weeks, and at 52 weeks of follow-up.

Comprehensive Update on Synthetic Aspects of Bosentan Derivatives.

Bosentan and its analogues were first reported as endothelin (ET) receptor antagonists in US patent No. 5, 292,740 in 1994. Bosentan synthesis has been reported by employing different methods from the reaction between (4,6-dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine and 4- (tert-butyl) benzenesulfonamide and 4-(tert-butyl)-N-(6-chloro-5-(2-methoxyphenoxy)-[2,2'- bipyrimidin]-4-yl) benzenesulfonamide in the form of different salts like potassium salt, ammonium salt, sodium salt, and free, on its reaction with ethylene glycol. Several changes have been observed in the chemistry of the involved intermediate synthesis, particularly coupling chemistry, to produce bosentan derivatives with high purity and yield.

Spotlight on the Mucormycosis Outbreak: A Deadly Fungal Infection That Followed the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic along with its treatment has brought myriad potential complications including the heightened risk of secondary fungal infections like mucormycosis. Mucormycosis is a rare angioinvasive fungal infection that has traditionally been highly fatal despite surgical intervention and antifungal medications. AIM: To re-evaluate the risk factors, epidemiology, and possible COVID-19-associated conditions on a larger sample size than the existing data. METHODOLOGY: We studied the possible risk factors, clinical presentations, treatment, and outcome of 203 patients with mucormycosis in a single-center retrospective-prospective observational study for three months at a tertiary care hospital after obtaining due permission from the institutional ethics committee. RESULTS: The mean age of patients was 52 ± 11.5 years, and 92.61% had a history of COVID-19 infection. Around 86.7% of patients were suffering from diabetes mellitus with 50% being already known cases whereas the other 50% developed post-COVID-19 infection; 65.02% of patients were administered corticosteroids during their COVID-19 treatment. About 51.72% of patients required hospital admission and among them, 16.25% of patients required ICU support. The mean oxygen saturation (SpO2) levels on admission were 84.61 ± 12.96%, and 38.92% of patients required mechanical respiratory support. The mean duration between COVID-19 infection and the onset of mucormycosis was 18.80 ± 16.61 days. The most common clinical presentations were facial pain and swelling (26.6%) and ophthalmic symptoms including eye swelling, pain, and ptosis (25.12%). Antifungal treatment was given to all the patients and 89.36% of the patients underwent surgical debridement of fungal mass. At the end of three months, 60.59% of the 188 patients survived with improvement, 13.30% had no improvement and/or deterioration of health, and 18.72% succumbed to mucormycosis. Intracranial involvement and leukocytosis were positively associated with mortality whereas surgical intervention was significant for positive outcomes at the end of three months in patients with mucormycosis (p<0.05). CONCLUSION: The sudden rise of mucormycosis during the second wave of COVID-19 can be attributed to uncontrolled blood sugar levels along with high corticosteroid usage as well as various nosocomial factors during the COVID-19 treatment. Early and aggressive treatment with surgical intervention and antifungal drugs can improve disease outcomes.

Development of novel bosentan analogues as endothelin receptor antagonists for pulmonary arterial hypertension.

Since decades, bosentan has been in use for the treatment of pulmonary arterial hypertension (PAH). However, chronic exposure to bosentan leads to the development of resistance, tolerance, and serious adverse effects that have restricted its usage in clinical practices. To surmount these limitations, some new bosentan derivatives have been synthesized and evaluated for their therapeutic efficacy in PAH. Molecular docking analyses of all the synthesized derivatives were carried out using the endothelin (ET) receptor. In addition, the inhibitory ability of synthesized derivatives was determined in in vitro assay employing an ET-1 human ELISA kit. Among the synthesized derivatives, three derivatives namely 17d, 16j, and 16h with higher docking scores and lower IC50 values were selected for determination of the magnitude of the binding force between the derivative and ET receptor using molecular dynamics (MD) simulations study. Further, these derivatives were subjected to in vivo studies using monocrotaline (MCT) induced PAH in rat model. Results of in vivo studies inferred that the derivatives exhibit impressive ability to reduce PAH. Besides, its protective role was also evidenced in hemodynamic and right ventricular hypertrophy analyses, histological analysis, cardiac biomarkers, hypoxia-inducible factor 1 alpha (HIF1α) levels, and biochemical studies. Furthermore, gene quantification by quantitative RT-PCR and Western blot analysis was also performed to examine its effect on the expression of key proteins in PAH. Notably, amongst three, derivative 16h exhibited the most encouraging results in molecular docking analysis, in vitro, in vivo, histopathological, biochemical, protein expression, and MD studies. Besides, derivative 16h also showed impressive pharmacokinetic features in ADMET analysis. In conclusion, derivative 16 h could act as a reliable ET receptor antagonist and requires further exploration to attain its therapeutic utility in PAH management.

An evaluation of trigger tool method for adverse drug reaction monitoring at a tertiary care teaching hospital.

OBJECTIVE: Trigger tool method (TTM) is an active surveillance method for adverse drug reaction (ADR) monitoring. The study aimed to evaluate TTM for ADR monitoring in indoor patients of the surgery department. MATERIALS AND METHODS: This prospective, observational study was conducted at the Department of Surgery of a Tertiary Care Teaching Hospital in Gujarat. Patients of either gender and more than 18 years of age admitted to two selected surgery units were enrolled with prior informed consent. Preliminary trigger tool list (PTTL) comprising 13 drug triggers (DTs), 13 patient triggers (PTs), 9 laboratory triggers (LTs), and 12 surgical module triggers (STs) were used. Patients were followed up till discharge to monitor the occurrence of triggers and adverse events. RESULTS: A total of 400 patients were included (male: female ratio of 2.3:1; mean age: 43.07 ± 16.4 years; and mean length of hospital stay: 5.75 ± 3.12 days). Of 400 patients, triggers were present in 359 patients (89.75%) and no trigger was observed in 41 patients (10.25%). Of the 47 triggers in PTTL, 24 triggers were observed 1155 times, of these 14 triggers lead to the detection of 49 ADRs in 43 patients. The rate of adverse drug events was 12.25/100 patients. DT was the most common trigger identified (81.64%). Positive predictive values (PPV) for PTs, STs, DTs, LTs were 26.88%, 23.07%, 10.3%, and 5.55%, respectively. The comprehensive PPV of PTTL was 11.97%. Modified trigger tool list consists of 14 triggers. CONCLUSION: TTM is an effective method of ADR monitoring in the surgery department. An awareness of TT helps better detection of ADRs.

Emergence of Cerebral Mucormycosis in the Post-COVID Period: A Detailed Analysis of Risk Factors, Clinical Progression, and Management of This Opportunistic Fungal Infection.

BACKGROUND: An epidemic of Mucorales was reported following the second wave of COVID-19 in India, and intracranial extension of the same was one of the most dreadful complications. METHODS: A total of 62 patients with cerebral mucormycosis were recruited and followed up till 12 weeks to evaluate the risk factors, incidence, clinical manifestations, management, and prognosis of cerebral mucormycosis. FINDINGS: A median age of 51.5 years with male predominance (74%) was noted. The majority of subjects reported a history of COVID infection (93.5%) and diabetes mellitus (83.87%). The first symptom of mucormycosis appeared after a mean period of 17.63 ± 8.9 days following COVID. Facial swelling and ptosis were the most common symptoms. Only 55% of patients had neurological presentations, and hemiparesis was the most common neurological sign (30.6%). Radiologically, the involvement of maxillary sinus (90.32%) and ethmoid sinus (87.10%) was commonly noted. Cerebral findings included temporal lobe (50%) and parietal lobe (30.06%) involvement, cavernous sinus thrombosis (30.06%), and internal carotid artery thrombosis (22.58%). Acute cerebral infarction was notable in 37% of subjects (p-value=0.0015, significant association with the outcome). Conventional and liposomal amphotericin B were used in 91.94% and 53.23% of patients, respectively. Retrobulbar amphotericin injections used in 11.3% of subjects significantly affected the outcome (p-value=0.03, significant). Posaconazole step-down therapy was used in 72.5% of subjects (p-value=0.0005, significant). Surgical interventions were performed in 53 (85.48%) subjects (p-value=0.004, significant). Functional endoscopic sinus surgery was the most common (in 64.52% of subjects), followed by maxillectomy (20.97% of subjects) and craniotomy (17.7% of subjects). At the end of 12 weeks, 33.87% of patients died and 59.68% were alive; the rest (6.45%) were lost to follow-up. INTERPRETATION: The absence or late presentation of neurological symptoms led to a delayed diagnosis of cerebral mucormycosis. The presence of acute cerebral infarction indicated a worse prognosis. However, there was a significant influence of step-down posaconazole therapy, retrobulbar amphotericin injections, and surgical intervention on the prognosis of cerebral mucormycosis.

An evaluation of trigger tool method for adverse drug reaction monitoring at a tertiary care teaching hospital.

OBJECTIVES: The objective of this study is to evaluate the trigger tool method (TTM) in detection, monitoring, and reporting of adverse drug reactions (ADRs) at Civil Hospital Ahmedabad, India. MATERIALS AND METHODS: A prospective, single-center, observational cum intervention study was conducted in two phases in the Department of Medicine over 15 months. In phase I, preliminary trigger tool list (PTTL) comprising 55 triggers was evaluated by pharmacologist in terms of detection of ADR in 400 patients and then, modified trigger tool list (MTTL) was prepared. In Phase II, the TTM using MTTL was compared with the spontaneous method of ADR monitoring after educational interventions in resident doctors of the two units of medicine department. RESULTS: Of the 55 triggers in PTTL, 34 triggers were observed in 327 patients, of which 19 triggers lead to the detection of 66 ADRs. The rate of ADEs was 16.5%/100 patients. Positive predictive value (PPV) of each trigger ranged from 0% to 100%. PPV for drug trigger, laboratory trigger, and PT was 14.4%, 4.5%, and 23.3%, respectively. Overall, PPV of PTTL was 19.27%. Sensitivity and specificity were 100% and 21.66%, respectively. MTTL consists of these 19 triggers. In Phase II, resident doctors reported 16 ADRs, using spontaneous method and 23 ADRs using MTTL. The rate of ADEs per 100 patients was 1.63 and 2.13, respectively, with these methods. A total of 105 ADRs were reported during both phases. CONCLUSION: TTM is an effective method of ADR reporting if it is utilized by a trained person. This method could be used as add-on method to spontaneous method to improve ADR reporting.

Early diagnosis of diaphragm palsy after pediatric cardiac surgery and outcome after diaphragm plication - A single-center experience.

OBJECTIVE: The aims of our prospective observational study were to evaluate the (1) reliability of clinical signs in the early detection of diaphragm palsy (DP); (2) reliability of ultrasonography using echo machine as a bedside tool for the diagnosis of DP; and (3) does early diaphragm plication result in the improved outcome? We also sought to determine the incidence and predominant risk factors for DP and diaphragm plication at our center. MATERIALS AND METHODS: This prospective observational study included patients with suspected DP from January 2015 to December 2018. Patients with suspected DP were initially evaluated by bedside ultrasonography using echo machine and confirmed by fluoroscopy. Diaphragm plication was considered for patients having respiratory distress, difficult weaning, or failed extubation attempt without any obvious cardiac or pulmonary etiology. Patients were followed for 3 months after discharge to assess diaphragm function. RESULTS: A total of 87 patients were suspected of DP based on clinical signs. DP was diagnosed in 61 patients on fluoroscopy. The median time from index operation to diagnosis was 10 (1-59) days. Diaphragm plication was done among 52 patients and not done in nine patients. Bedside ultrasonography using echo machine was 96.7% sensitive and 96.15% specific in diagnosing DP. Early plication (<14 days) significantly reduced the need for nasal continuous positive airway pressure (65% vs. 96%, P = 0.02), duration of mechanical ventilation (12 vs. 25 days, P = 0.018), intensive care unit (ICU) stay (25 days vs. 39 days, P = 0.019), and hospital stay (30 days vs. 46 days, P = 0.036). CONCLUSION: Hoover's sign and raised hemidiaphragm on chest X-ray are the most specific clinical signs to suspect unilateral DP. Bedside ultrasonography using an echo machine is a good diagnostic investigation comparable to fluoroscopy. Early plication facilitates weaning from the ventilator and thereby decreases the ICU stay and hospital stay.

Early treatment outcome of bedaquiline plus optimised background regimen in drug resistant tuberculosis patients.

AIMS: Bedaquiline (BDQ) has been recently approved for drug resistant tuberculosis with active drug safety monitoring under programmatic condition. The present study was conducted to evaluate safety, tolerability and efficacy of bedaquiline plus optimised background regimen. METHODS: A prospective study was conducted on cohort of pre-extensively drug resistant (XDR) and XDR pulmonary TB patients. Eligible patients were closely monitored for cardiac safety, adverse events (AEs), clinical and microbiological improvement during BDQ (6 months) and post BDQ phase for twelve months. RESULTS: Of 127 patients enrolled, a significant increase in mean QTc interval was observed on 13th day and 3rd week as compared to baseline (p < 0.0001). Mean maximum increase of QTc was 37.92ms (95% CI, 14.1-61.74ms). Concomitant anti-TB medications, age, gender, low body mass index (BMI) had significant effect on QTc prolongation (p < 0.0001, p < 0.05). However, none of the patient required discontinuation of BDQ. Majority of AEs (86.3%) were non-serious and not preventable 108 (87.1%). The median time for sputum-culture conversion was 40.89 ± 3.5 days (95% CI, 34-48 days) and the treatment outcome was successful in 102 (80.3%) patients with negative sputum culture conversion. CONCLUSIONS: Bedaquiline containing regimen achieved favourable outcome. Although, bedaquiline along with concomitant anti-TB medications has the potential to prolong QTc interval, the benefit certainly outweighs the risk. This calls for a through pre-treatment cardiovascular and biochemical evaluation as a preventive measure and appropriate selection of patients for safe use of BDQ and successful outcome.

Risk Factors for Delayed Extubation after Ventricular Septal Defect Closure: a Prospective Observational Study.

OBJECTIVE: The objective of our study was to determine the feasibility of early extubation and to identify the risk factors for delayed extubation in pediatric patients operated for ventricular septal defect closure. METHODS: A prospective, observational study was carried out at our Institute. This study involved consecutive 135 patients undergoing ventricular septal defect closure. Patients were extubated if feasible within six hours after surgery. Based on duration of extubation, patients were divided two groups: Group 1= extubation time ≤ 6 hours, Group 2= extubation time >6 hours. RESULTS: A total of 99 patients were in Group 1 and 36 patients in Group 2. Duration of ventilation was 4.4±0.9 hours in Group 1 and 25.9±24.9 hours in Group 2 (P<0.001). Univariate analysis showed that young age, low weight, low partial pressure of oxygen, trisomy 21, multiple ventricular septal defect, high vasoactive inotropic score, transient heart block and low cardiac output syndrome were associated with delayed extubation. However, regression analysis revealed that only trisomy 21 (OR: 0.248; 95%CI: 0.176-0.701; P=0.001), low cardiac output syndrome (OR: 0.291; 95%CI: 0.267-0.979; P=0.001), multiple ventricular septal defect (OR: 0.243; 95%CI: 0.147-0.606; P=0.002) and vasoactive inotropic score (OR: 0.174 95%CI: 0.002-0.062; P=0.039) are strongest predictors for delayed extubation. CONCLUSION: Trisomy 21, low cardiac output syndrome, multiple ventricular septal defect and high vasoactive inotropic score are significant risk factors for delay in extubation. Age, weight, pulmonary artery hypertension, size of ventricular septal defect, aortic cross-clamp and cardiopulmonary bypass time did not affect early extubation.

An analysis of serious adverse drug reactions at a tertiary care teaching hospital.

OBJECTIVE: The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs) such as clinical presentation, causality, severity, and preventability occurring in a hospital setting. MATERIALS AND METHODS: All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization -Uppsala Monitoring Center (WHO-UMC) criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo's algorithm), severity (Hartwig and Siegel scale), and preventability (Schumock and Thornton criteria). RESULTS: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%). The common causal drug group was antitubercular (129, 34.4%) followed by antiretroviral (76, 20.3%) agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7%) followed by hospitalization (158, 42.1%). Majority of the serious ADRs were continuing (191, 50.9%) at the time of reporting, few recovered (101, 26.9%), and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8%) followed by probable (173, 46.1%) in nature. CONCLUSION: Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management.

Evaluation of impact of teaching clinical pharmacology and rational therapeutics to medical undergraduates and interns.

OBJECTIVES: To find out the impact of teaching clinical pharmacology and rational therapeutics (CPT) to medical undergraduates (UGs) and interns. MATERIALS AND METHODS: This cross-sectional, prospective study was conducted on three UGs batches and interns using two pretested validated structured questionnaires, modified from the work of Tobaiqy et al. The study was approved by the Institutional Ethics Committee. ANOVA and Chi-square test were used for statistical analysis. The value of P < 0.05 was considered statistically significant. RESULTS: A total of 379 UGs and 96 interns participated in this study. Mean knowledge score of interns was significantly reduced as compared to UGs (P < 0.0001). A significant increase in confidence for unsupervised prescribing of nonsteroidal anti-inflammatory drugs (99%), oral rehydration salt, iron salts was perceived among interns as compared to UGs (P < 0.05). However, 63.5% confessed problems in selection of drugs, drug-drug interactions, prescribing in special patient population. Although they were confident prescribing fixed dose combination for adult patients (89.5%), majority were hesitant to prescribe opioids (77%), steroids (76%), vaccines (75%), and antihypertensives (62%). CONCLUSION: The theoretical CPT teaching transfers knowledge to UGs; however, it is not retained in internship and does not adequately prepare interns to prescribe safe and rational drugs.

Recurrent Left Atrial Myxoma in a Young Patient: A Rare Entity.

Recurrence of atrial myxoma arising from the site other than inter-atrial septum is quite rare, which is more common in familial than sporadic cases. We here in present a case of 15-year-old young female who presented with recurrence of left atrial (LA) myxoma from unusual site - posterior LA wall after 3 years without any constitutional symptoms, which is the hallmark of recurrence. Complete removal of underlying atrial septum with atrial wall for recurrence prevention is the dictum in primary operation for tumour removal.

Horseshoe lung with cor triatriatum and partial atrioventricular canal defect.

Cor triatriatum with partial atrioventricular canal defect is a rare congenital cardiac anomaly. We report a case of cor triatriatum and partial atrioventricular canal defect in association with horseshoe lung.

A rare variety of mixed total anomalous pulmonary venous connection.

We describe a rare case of mixed supra- and infracardiac total anomalous pulmonary venous connection in a 2-month-old boy weighing 2.3 kg who was admitted with central cyanosis. Although the surgical repair was successful, the child died due to pulmonary hypertensive crisis.

Risk factors for delayed extubation after ventricular septal defect closure: a prospective observational study

Objective: The objective of our study was to determine the feasibility of early extubation and to identify the risk factors for delayed extubation in pediatric patients operated for ventricular septal defect closure. Methods: A prospective, observational study was carried out at our Institute. This study involved consecutive 135 patients undergoing ventricular septal defect closure. Patients were extubated if feasible within six hours after surgery. Based on duration of extubation, patients were divided two groups: Group 1= extubation time ≤ 6 hours, Group 2= extubation time >6 hours. Results: A total of 99 patients were in Group 1 and 36 patients in Group 2. Duration of ventilation was 4.4±0.9 hours in Group 1 and 25.9±24.9 hours in Group 2 (P<0.001). Univariate analysis showed that young age, low weight, low partial pressure of oxygen, trisomy 21, multiple ventricular septal defect, high vasoactive inotropic score, transient heart block and low cardiac output syndrome were associated with delayed extubation. However, regression analysis revealed that only trisomy 21 (OR: 0.248; 95%CI: 0.176-0.701; P=0.001), low cardiac output syndrome (OR: 0.291; 95%CI: 0.267-0.979; P=0.001), multiple ventricular septal defect (OR: 0.243; 95%CI: 0.147-0.606; P=0.002) and vasoactive inotropic score (OR: 0.174 95%CI: 0.002-0.062; P=0.039) are strongest predictors for delayed extubation. Conclusion: Trisomy 21, low cardiac output syndrome, multiple ventricular septal defect and high vasoactive inotropic score are significant risk factors for delay in extubation. Age, weight, pulmonary artery hypertension, size of ventricular septal defect, aortic cross-clamp and cardiopulmonary bypass time did not affect early extubation.

An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital.

OBJECTIVES: Spontaneous reporting is an important tool in pharmacovigilance. However, its success depends on cooperative and motivated prescribers. Under-reporting of adverse drug reactions (ADRs) by prescribers is a common problem. The present study was undertaken to evaluate the knowledge, attitude, and practices (KAP) regarding ADR reporting among prescribers at the Civil Hospital, Ahmedabad, to get an insight into the causes of under-reporting of ADRs. MATERIALS AND METHODS: A pretested KAP questionnaire comprising of 15 questions (knowledge 6, attitude 5, and practice 4) was administered to 436 prescribers. The questionnaires were assessed for their completeness (maximum score 20) and the type of responses regarding ADR reporting. Microsoft Excel worksheet (Microsoft Office 2007) and Chi-Square test were used for statistical analysis. RESULTS: A total of 260 (61%) prescribers completed the questionnaire (mean score of completion 18.04). The response rate of resident doctors (70.7%) was better than consultants (34.5%) (P < 0.001). ADR reporting was considered important by 97.3% of the respondents; primarily for improving patient safety (28.8%) and identifying new ADRs (24.6%). A majority of the respondents opined that they would like to report serious ADRs (56%). However, only 15% of the prescribers had reported ADRs previously. The reasons cited for this were lack of information on where (70%) and how (68%) to report and the lack of access to reporting forms (49.2%). Preferred methods for reporting were e-mail (56%) and personal communication (42%). CONCLUSION: The prescribers are aware of the ADRs and the importance of their reporting. However, under reporting and lack of knowledge about the reporting system are clearly evident. Creating awareness about ADR reporting and devising means to make it easy and convenient may aid in improving spontaneous reporting.